Cytotoxic activity of tumor necrosis factor is inhibited by amiloride derivatives without involvement of the Na+/H+ antiporter.

Cytotoxicity of tumor necrosis factor (TNF) on L929s cells was efficiently blocked by several amiloride analogs but not by amiloride itself. This protection did not require RNA or protein synthesis. Na+/H+ antiporter-negative L-M(TK-) cells (LAP) could be killed by TNF, showing that the Na+/H+ exchanger is not required for TNF-cytotoxicity. Similar protection against TNF-mediated cell lysis by amiloride derivatives was found for LAP and L929s cells, excluding a blockade of the Na+/H+ antiporter as the cause of the protection against TNF by these agents.